Nature biotechnologyOct 23, 2025

Using and Improving Retrons for Accurate Genome Editing

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 28, 2026

Abstract

Essence

Engineered retrons provide a genetically encoded way to support precise genome editing in mammalian cells and vertebrates.

Evidence

This genome-editing platform study combined metagenomic discovery, functional screening, and engineering in mammalian cells and vertebrate embryos, showing retron editors with efficiencies comparable to single-stranded oligodeoxynucleotide donors, compatibility with Cas12a and Cas9 nickase, split GFP tagging, and all-RNA delivery.

Caveat

The work establishes a versatile editing tool but is mainly a platform study, not evidence of therapeutic benefit or long-term in vivo safety.

Simplified

Retrons can produce multicopy single-stranded DNA in cells through self-primed reverse transcription. However, their potential for inserting genetic cargos in eukaryotes remains largely unexplored. Here we report the discovery and engineering of highly efficient retron-based gene editors for mammalian cells and vertebrates. Through bioinformatic analysis of metagenomic data and functional screening, we identify retron reverse transcriptases that are highly active in mammalian cells. Rational design further improves the editing efficiency to levels comparable with conventional single-stranded oligodeoxynucleotide donors but from a genetically encoded cassette. Retron editors exhibit robust activity with Cas12a nuclease and Cas9 nickase, expanding the genomic target scope and bypassing the need for a DNA double-stranded break. Using a rationally engineered retron editor, we incorporate a split GFP epitope tag for live-cell imaging. Lastly, we develop an all-RNA delivery strategy to enable DNA-free gene editing in cells and vertebrate embryos. This work establishes retron editors as a versatile and efficient tool for precise gene editing.